Leukotriene antagonists

Abstract

Compounds having the formula: ##STR1## are antagonists of leukotrienes of C 4 , D 4 and E 4 , the slow reacting substance of anaphylaxis. These compounds are useful as anti-asthmatic, anti-allergic and anti-inflammatory agents.

What is claimed is: 
     
       1. A compound having the formula Ia: ##STR23## wherein each R is independently H, alkyl of 1 to 6 carbon atoms which may be straight chain or branched; trifluoromethyl; halogen; or N(R 4 ) 2  ; each R' is independently R 4  or OR 4  ;   Y' is oxygen, sulfur, sulfoxide or sulfone;   R 2  is ##STR24## wherein: each R 4  is independently H or alkyl of 1 to 6 carbon atoms which may be straight chain or branched;   each R 6  is independently H or alkyl of 1 to 4 carbons;   each R 7  is independently H, OH, or alkyl of 1 to 4 carbons;   R 5  is COOR 4  ;   r and q are each independently 0 to 3; and   p is 0 or 1;   R 3  is alkyl of 1 to 6 carbon atoms which may be straight chain or branched; or alkenyl of 3 to 6 carbon atoms which may be straight chain or branched;   R 9  is alkyl of 1 to 6 carbon atoms which may be straight chain or branched; or a pharmaceutically acceptable salt or acid addition salt thereof.   
     
     
       2. The compounds of claim 1: trans,trans-3-(4-acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxy-1-(4-carboxymethylphenylthio)cyclohexane;   trans,trans-3-(4-acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxy-1-(4-(3-carboxy-1-oxopropyl)-2-fluorophenylthio)cyclohexane;   trans,trans-1-(4-acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxy-1-(4-(3-carboxy-1-oxopropyl)-2-fluorophenylthio)cyclohexane-S-oxide;   trans,trans-3-(4-acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxy-1-(4-(3-carboxy-1-oxopropyl)phenylthio)cyclohexane;   trans,trans-3-(4-acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxy-1-(4-carboxymethylphenoxy)cyclohexane;   cis-3-(4-acetyl-3-hydroxy-2-propylphenoxy)-1-(4-(3-carboxy-1-oxopropyl)phenylthio)cyclohexane; and   trans-3-(4-acetyl-3-hydroxy-2-propylphenoxy)-1-(4-carboxymethylphenylthio)cyclohexane;   trans-3-(4-acetyl-3-hydroxy-2-propylphenoxy)-1-(4-carboxymethyl-2-bromo phenoxy)cyclohexane;   cis-3-(4-acetyl-3-hydroxy-2-propylphenoxy)-1-(4-carboxymethyl-2-bromophenoxy)cyclohexane;   trans-3-(4-acetyl)-3-hydroxy-2-propylphenoxy)-1-(4-(3-carboxy-1-oxopropyl)phenoxy)cyclohexane;   cis-3-(4-acetyl-3-hydroxy-2-propylphenoxy)-1-(4-(3-carboxy-1-oxo-propyl)phenoxy)cyclohexane;   trans-3-(4-acetyl-3-hydroxy-2-propylphenoxy)-1-(4-carboxymethylphenoxy)-cyclohexane;   cis-3-(4-acetyl-3-hydroxy-2-propylphenoxy)-1-(4-carboxymethylphenoxy)-cyclohexane.   
     
     
       3. A composition for antagonizing leukotriene action in a mammal comprising an effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier. 
     
     
       4. A method of antagonizing leukotriene action in a mammal which comprises administering to a mammal an amount of a compound of claim 1 effective as a leukotriene antagonist.